Yvonne Romero's long term career goal is to decrease the mortality rate of esophageal adenocarcinoma. Yvonne is a Harvard undergraduate who completed a 3-year Gastroenterology fellowship at Mayo in 1996, matriculated into the Clinical Epidemiology and Biostatistics Program at McMaster University in 1997, was the first Mayo Fellow in Diseases of the Esophagus in 1998, who joined the staff at Mayo in May 1999. Her clinical mentor, Alan J. Cameron, MD, is a recognized authority on Barrett's esophagus, a premalignant disorder. They have been addressing the question of familial gastroesophageal reflux disease and Barrett's esophagus since 1994. Their first project, which showed aggregation of reflux symptoms in families of probands with Barrett's esophagus and esophageal adenocarcinoma (but not solo reflux esophagitis), was published in Gastroenterology in 1997. In the Barrett's Esophagus Genomic Study, for which Dr. Romero acts as primary investigator, 96 families with 3 or more effected persons have already been identified. A separate pilot study showed a trend of increased Barrett's esophagus prevalence among symptomatic relatives of probands with Barrett's compared to controls. Doctor Romero's immediate goals are to, 1) determine the risk of Barrett's esophagus and reflux esophagitis, the presumed precursor of Barrett's, among relatives of Barrett's probands compared to age-, sex-, medication- and symptom- matched controls without significant family history; and 2) collect blood from high- prevalence Barrett's esophagus families. Her intermediate goals are to 1) carry out a genome screen to map the chromosomal location of the gene(s) responsible for the phenotypes of reflux esophagitis and Barrett's esophagus using linkage analysis; 2) detect genetic heterogeneity as there is likely more than one major gene involved; and 3) fine map the genetic region(s) identified through linkage analysis, to identify the smallest genomic segment that contains the gene(s). To pursue this line of evidence in a scientifically stringent manner, Dr. Romero has been enrolled in genetic epidemiology coursework at the University of Minnesota since February 1999 and will continue to do so as supported by this award.